PubMed:21523445
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/21523445","sourcedb":"PubMed","sourceid":"21523445","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/21523445","text":"Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer.\nThe potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.3%), which can be reversed by treatment with demethylation agent 5-aza-2'-deoxycytidine (Aza), but not HDAC inhibitor trichostatin A. In addition, KL expression is markedly downregulated in colorectal carcinoma tissues when compared to the adjacent nontumor tissues (n=25, p\u003c0.001). The methylation of the KL gene promoter was frequently detected in primary tumor tissues (34/40, 85%) when compared with adjacent nontumor colon tissues. Furthermore, ectopic expression of KL led to the cell proliferation inhibition of colon cancer cell lines via the induction of cell apoptosis and S-phase cell cycle arrest. Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_21523445_1_0","span":{"begin":158,"end":164},"obj":"expanded"},{"id":"SS2_21523445_1_0","span":{"begin":166,"end":168},"obj":"abbr"},{"id":"SS1_21523445_2_0","span":{"begin":431,"end":448},"obj":"expanded"},{"id":"SS2_21523445_2_0","span":{"begin":450,"end":453},"obj":"abbr"},{"id":"SS1_21523445_3_0","span":{"begin":609,"end":631},"obj":"expanded"},{"id":"SS2_21523445_3_0","span":{"begin":633,"end":636},"obj":"abbr"}],"relations":[{"id":"AE1_21523445_1_0","pred":"abbreviatedTo","subj":"SS1_21523445_1_0","obj":"SS2_21523445_1_0"},{"id":"AE1_21523445_2_0","pred":"abbreviatedTo","subj":"SS1_21523445_2_0","obj":"SS2_21523445_2_0"},{"id":"AE1_21523445_3_0","pred":"abbreviatedTo","subj":"SS1_21523445_3_0","obj":"SS2_21523445_3_0"}],"attributes":[{"subj":"SS1_21523445_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_21523445_1_0","pred":"source","obj":"Allie"},{"subj":"SS1_21523445_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_21523445_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_21523445_3_0","pred":"source","obj":"Allie"},{"subj":"SS2_21523445_3_0","pred":"source","obj":"Allie"}]},{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":511,"end":516},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":966,"end":971},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":1063,"end":1068},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":281,"end":285},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":755,"end":762},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":802,"end":809},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":908,"end":915},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T8","span":{"begin":972,"end":979},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T9","span":{"begin":273,"end":279},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T8","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T9","pred":"source","obj":"performance-test"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":255,"end":262},"obj":"HP_0002664"},{"id":"T2","span":{"begin":291,"end":306},"obj":"HP_0030079"},{"id":"T3","span":{"begin":300,"end":306},"obj":"HP_0002664"},{"id":"T4","span":{"begin":363,"end":368},"obj":"HP_0002664"},{"id":"T5","span":{"begin":442,"end":448},"obj":"HP_0002664"},{"id":"T6","span":{"begin":511,"end":523},"obj":"HP_0003003"},{"id":"T7","span":{"begin":511,"end":523},"obj":"HP_0100273"},{"id":"T8","span":{"begin":517,"end":523},"obj":"HP_0002664"},{"id":"T9","span":{"begin":902,"end":907},"obj":"HP_0002664"},{"id":"T10","span":{"begin":1063,"end":1075},"obj":"HP_0003003"},{"id":"T11","span":{"begin":1063,"end":1075},"obj":"HP_0100273"},{"id":"T12","span":{"begin":1069,"end":1075},"obj":"HP_0002664"},{"id":"T13","span":{"begin":1278,"end":1283},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"},{"subj":"T7","pred":"source","obj":"PubmedHPO"},{"subj":"T8","pred":"source","obj":"PubmedHPO"},{"subj":"T9","pred":"source","obj":"PubmedHPO"},{"subj":"T10","pred":"source","obj":"PubmedHPO"},{"subj":"T11","pred":"source","obj":"PubmedHPO"},{"subj":"T12","pred":"source","obj":"PubmedHPO"},{"subj":"T13","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1195,"end":1197},"obj":"gene:9365"},{"id":"T1","span":{"begin":1303,"end":1306},"obj":"disease:C0009402"},{"id":"T2","span":{"begin":1195,"end":1197},"obj":"gene:9365"},{"id":"T3","span":{"begin":1303,"end":1306},"obj":"disease:C1527249"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":122},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":123,"end":307},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":308,"end":455},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":456,"end":677},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":678,"end":826},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":827,"end":980},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":981,"end":1153},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1154,"end":1307},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":122},"obj":"Sentence"},{"id":"T2","span":{"begin":123,"end":307},"obj":"Sentence"},{"id":"T3","span":{"begin":308,"end":455},"obj":"Sentence"},{"id":"T4","span":{"begin":456,"end":677},"obj":"Sentence"},{"id":"T5","span":{"begin":678,"end":826},"obj":"Sentence"},{"id":"T6","span":{"begin":827,"end":980},"obj":"Sentence"},{"id":"T7","span":{"begin":981,"end":1153},"obj":"Sentence"},{"id":"T8","span":{"begin":1154,"end":1307},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"}]},{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":273,"end":279},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":281,"end":285},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":511,"end":516},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":966,"end":971},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T5","span":{"begin":1063,"end":1068},"obj":"http://purl.obolibrary.org/obo/UBERON_0001155"},{"id":"PD-UBERON-AE-B_T6","span":{"begin":755,"end":762},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T7","span":{"begin":802,"end":809},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T8","span":{"begin":908,"end":915},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T9","span":{"begin":972,"end":979},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T3","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T4","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T5","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T6","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T7","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T8","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T9","pred":"source","obj":"UBERON-AE"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T327","span":{"begin":0,"end":6},"obj":"gene:9365"},{"id":"T328","span":{"begin":104,"end":121},"obj":"disease:C0009402"},{"id":"T329","span":{"begin":158,"end":164},"obj":"gene:9365"},{"id":"T330","span":{"begin":291,"end":306},"obj":"disease:C0007847"},{"id":"T331","span":{"begin":166,"end":168},"obj":"gene:9365"},{"id":"T332","span":{"begin":647,"end":651},"obj":"gene:9734"},{"id":"T333","span":{"begin":511,"end":523},"obj":"disease:C0007102"},{"id":"T334","span":{"begin":1016,"end":1018},"obj":"gene:9365"},{"id":"T335","span":{"begin":1063,"end":1075},"obj":"disease:C0007102"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T327","obj":"T328"},{"id":"R2","pred":"associated_with","subj":"T327","obj":"T328"},{"id":"R3","pred":"associated_with","subj":"T329","obj":"T330"},{"id":"R4","pred":"associated_with","subj":"T329","obj":"T330"},{"id":"R5","pred":"associated_with","subj":"T329","obj":"T330"},{"id":"R6","pred":"associated_with","subj":"T331","obj":"T330"},{"id":"R7","pred":"associated_with","subj":"T331","obj":"T330"},{"id":"R8","pred":"associated_with","subj":"T331","obj":"T330"},{"id":"R9","pred":"associated_with","subj":"T332","obj":"T333"},{"id":"R10","pred":"associated_with","subj":"T332","obj":"T333"},{"id":"R11","pred":"associated_with","subj":"T334","obj":"T335"},{"id":"R12","pred":"associated_with","subj":"T334","obj":"T335"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T327","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T328","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T329","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T330","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T331","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T332","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T333","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T334","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T335","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"21523445-0#0#6#gene9365","span":{"begin":0,"end":6},"obj":"gene9365"},{"id":"21523445-0#104#121#diseaseC0009402","span":{"begin":104,"end":121},"obj":"diseaseC0009402"},{"id":"21523445-0#104#121#diseaseC1527249","span":{"begin":104,"end":121},"obj":"diseaseC1527249"},{"id":"21523445-1#35#41#gene9365","span":{"begin":158,"end":164},"obj":"gene9365"},{"id":"21523445-1#43#45#gene9365","span":{"begin":166,"end":168},"obj":"gene9365"},{"id":"21523445-1#168#183#diseaseC0007847","span":{"begin":291,"end":306},"obj":"diseaseC0007847"},{"id":"21523445-1#168#183#diseaseC0302592","span":{"begin":291,"end":306},"obj":"diseaseC0302592"},{"id":"21523445-1#168#183#diseaseC4048328","span":{"begin":291,"end":306},"obj":"diseaseC4048328"},{"id":"21523445-1#168#183#diseaseC0007847","span":{"begin":291,"end":306},"obj":"diseaseC0007847"},{"id":"21523445-1#168#183#diseaseC0302592","span":{"begin":291,"end":306},"obj":"diseaseC0302592"},{"id":"21523445-1#168#183#diseaseC4048328","span":{"begin":291,"end":306},"obj":"diseaseC4048328"},{"id":"21523445-3#191#195#gene9734","span":{"begin":647,"end":651},"obj":"gene9734"},{"id":"21523445-3#55#67#diseaseC0007102","span":{"begin":511,"end":523},"obj":"diseaseC0007102"},{"id":"21523445-3#55#67#diseaseC0699790","span":{"begin":511,"end":523},"obj":"diseaseC0699790"},{"id":"21523445-6#35#37#gene9365","span":{"begin":1016,"end":1018},"obj":"gene9365"},{"id":"21523445-6#82#94#diseaseC0007102","span":{"begin":1063,"end":1075},"obj":"diseaseC0007102"},{"id":"21523445-6#82#94#diseaseC0699790","span":{"begin":1063,"end":1075},"obj":"diseaseC0699790"}],"relations":[{"id":"0#6#gene9365104#121#diseaseC0009402","pred":"associated_with","subj":"21523445-0#0#6#gene9365","obj":"21523445-0#104#121#diseaseC0009402"},{"id":"0#6#gene9365104#121#diseaseC1527249","pred":"associated_with","subj":"21523445-0#0#6#gene9365","obj":"21523445-0#104#121#diseaseC1527249"},{"id":"35#41#gene9365168#183#diseaseC0007847","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC0007847"},{"id":"35#41#gene9365168#183#diseaseC0302592","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC0302592"},{"id":"35#41#gene9365168#183#diseaseC4048328","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC4048328"},{"id":"35#41#gene9365168#183#diseaseC0007847","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC0007847"},{"id":"35#41#gene9365168#183#diseaseC0302592","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC0302592"},{"id":"35#41#gene9365168#183#diseaseC4048328","pred":"associated_with","subj":"21523445-1#35#41#gene9365","obj":"21523445-1#168#183#diseaseC4048328"},{"id":"43#45#gene9365168#183#diseaseC0007847","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC0007847"},{"id":"43#45#gene9365168#183#diseaseC0302592","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC0302592"},{"id":"43#45#gene9365168#183#diseaseC4048328","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC4048328"},{"id":"43#45#gene9365168#183#diseaseC0007847","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC0007847"},{"id":"43#45#gene9365168#183#diseaseC0302592","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC0302592"},{"id":"43#45#gene9365168#183#diseaseC4048328","pred":"associated_with","subj":"21523445-1#43#45#gene9365","obj":"21523445-1#168#183#diseaseC4048328"},{"id":"191#195#gene973455#67#diseaseC0007102","pred":"associated_with","subj":"21523445-3#191#195#gene9734","obj":"21523445-3#55#67#diseaseC0007102"},{"id":"191#195#gene973455#67#diseaseC0699790","pred":"associated_with","subj":"21523445-3#191#195#gene9734","obj":"21523445-3#55#67#diseaseC0699790"},{"id":"35#37#gene936582#94#diseaseC0007102","pred":"associated_with","subj":"21523445-6#35#37#gene9365","obj":"21523445-6#82#94#diseaseC0007102"},{"id":"35#37#gene936582#94#diseaseC0699790","pred":"associated_with","subj":"21523445-6#35#37#gene9365","obj":"21523445-6#82#94#diseaseC0699790"}],"attributes":[{"subj":"21523445-0#0#6#gene9365","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-0#104#121#diseaseC0009402","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-0#104#121#diseaseC1527249","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#35#41#gene9365","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#43#45#gene9365","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC0007847","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC0302592","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC4048328","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC0007847","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC0302592","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-1#168#183#diseaseC4048328","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-3#191#195#gene9734","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-3#55#67#diseaseC0007102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-3#55#67#diseaseC0699790","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-6#35#37#gene9365","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-6#82#94#diseaseC0007102","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21523445-6#82#94#diseaseC0699790","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#ece093","default":true},{"id":"performance-test","color":"#c693ec"},{"id":"PubmedHPO","color":"#93ecac"},{"id":"DisGeNET","color":"#ec9393"},{"id":"sentences","color":"#93adec"},{"id":"UBERON-AE","color":"#c8ec93"},{"id":"DisGeNet-2017-sample","color":"#ec93e2"},{"id":"DisGeNET5_gene_disease","color":"#93ecdc"}]}]}}